New information will be sought in two areas: 1. Expression and replication of the viral genome, and control of these processes; and 2. Pathogenicity of viral protein products through specific interactions with host cell components. Appropriate model systems are essential for the analysis of mechanisms in cytocidal, moderate, and tumorigenic virus-cell interactions. We propose to investigate in detail the mechanisms whereby picorna and reoviruses alter cellular functions and structure, and employ other viruses to extend analysis of particular aspects of virus-cell interaction. In conjunction with direct biochemical and electron microscopic investigations, extensive use will be made of genetic variants of viruses and cells, and of inhibitors of viral and cellular processes. The role of host-dependent restriction of virus multiplication in viral infections and disease will be approached from two viewpoints: 1. Steps in viral biosynthesis which are subject to restriction or modification by the host cell, 2. Host cell components or processes which determine extent of replication of a virus in a host. The question of the precise nature of virus-induced alterations in cellular biosynthesis will be investigated. In particular, the problem of control of initiation of cellular DNA synthesis will be studied in infections with viruses of diverse pathogenic potentialities.